My laboratory studies the molecular and neural basis of endogenous daily (circadian) rhythms in mammals. We focus upon the suprachiasmatic nucleus of the hypothalamus (SCN), a master pacemaker critical not only to general activity rhythms but also to the estrous cycle, the rhythmic secretion of many hormones, and seasonal breeding. The restriction of reproduction to a particular time of year depends upon the discrimination of daylength. The circadian system accomplishes this by SCN-regulated secretion of the hormone melatonin by the pineal gland, and detection of melatonin duration using highly specific cell membrane receptors in the brain. We analyze gene expression in the SCN by methods which include multiple label in situ hybridization and immunocytochemistry. Retinal input triggers the expression of immediate early genes, including analogs of the Drosophila period gene, per, in order to shift the phase of the circadian clock. Nightly secretion of melatonin provides another cue which may reset the clock and allow the detection of daylength by the SCN. We are characterizing specific SCN cell types which participate in generation of the circadian oscillation, its synchronization with the outside world, and communication with the rest of the brain and ultimately the entire animal. The appropriate timing of ovulation is controlled not only by signals from the ovary, but also by the circadian clock. We find that projections of the SCN contact not only neurons which contain estrogen receptor, but also those which regulate the pituitary. Furthermore, estrogen-responsive cells reciprocate to regulate circadian rhythms through their projections to the SCN. What seasonal changes in brain function drive fluctuations in reproduction, sexual behavior, and energy metabolism? We find that daylength regulates the incorporation of neurons born in adulthood. This effect is not attributable to changes in the secretion of gonadal hormones. Daylength and testosterone interact to regulate androgen and opiate receptor expression in hamster brain in ways which may explain seasonal changes in sexual behavior and endocrine feedback. We are discovering mechanisms by which the nervous system integrates environmental (photoperiodic) information with
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Does the Precision of a Biological Clock Depend Upon its Period? Effects of the Duper and Tau Mutations in Syrian Hamsters, PLOS One (2012)
Mutations which alter the feedback loops that generate circadian rhythms may provide insight into their...
Duper: a mutation that shortens hamster circadian period (with S Monecke, J Brewer McKinley, and S Krug), Journal of Biological Rhythms (2011)
Three animals born to homozygous tau mutant (τss, “super short”) Syrian hamsters showed extremely short...
Effects of the Duper Mutation on Circadian Responses to Light (with S. Krug, J. M. Brewer, and A. S. Bois), Journal of Biological Rhythms (2011)
The circadian mutation duper in Syrian hamsters shortens the free-running circadian period (τDD) by 2...
Circadian Organization oftau Mutant Hamsters: Aftereffects and Splitting (with M. K. Costello and J. M. Brewer), Journal of Biological Rhythms (2007)
Homozygous tau mutant (τss) hamsters show an extremely short (20 h) circadian period (τ) that...
Suprachiasmatic Regulation of Circadian Rhythms of Gene Expression in Hamster Peripheral Organs: Effects of Transplanting the Pacemaker (with H Guo, J. M. Brewer, and M. N. Lehman), Journal of Neuroscience (2006)
Neurotransplantation of the suprachiasmatic nucleus (SCN) was used to assess communication between the central circadian...